The proposed research project is aimed at obtaining a fuller understanding of the physiological mechanisms controlling parietal cell function. An isolated parietal cell system was chosen because it allows the parietal cell to be removed from the influences of its mucosal environment and separated from other cellular elements. During the initial phases of this work, methods have been developed for the dispersion of fundic mucosal cells; for monitoring the physiological response of the parietal cell using oxygen uptake and morphological transformation; and for determining the cyclic AMP response to stimulation. Methods are being developed for separation of an enriched parietal cell fraction, for determining the cyclic GMP response to stimulation, and for studying the direct interaction of radiolabeled hormones with their specific cell receptors. With these methods the following problems will be investigated: 1) the direct actions of histamine, gastrin, and cholinergic agents on parietal cells and the interactions that occur between these agents, 2) the effects of anticholinergics and H2-receptor antagonists on secretagogue action and interaction, 3) the effects of other gastrointestinal hormones and other agents on basal and stimulated parietal cell function, 4) the comparison of biological potency of gastrin analogues, and 5) evaluation of the role of cyclic nucleotides in mediating hormone action on parietal cells. The ultimate objectives of this research will not only be to obtain a more complete understanding of basic parietal cell physiology but also to gain insight into pathophysiological mechanisms of peptic ulcer disease and into potential therapeutic modalities for treating ulcer disease.